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Triple Killer

Physicians create new cells to stave off common viruses that threaten transplant patients.
By Al Staropoli

After seeing many of her bone marrow transplant patients become seriously ill, physician Catherine Bollard decided to fashion a new immune cell to fight common viruses.

“We see viral infection in about 70 percent of our patients after transplant,” says Bollard, a pediatric hematologist at the Texas Children’s Cancer Center. The viruses, which are generally benign to healthy patients, can be life-threatening to transplant patients and others with compromised immune systems.

Transplant patients have traditionally been treated with antiviral drugs to prevent infections, but these drugs are expensive, have many toxic side effects, and need to be administered intravenously every day for approximately four months. In addition, when these medicines are stopped, patients are still prone to viral infections.

Instead of using antiviral drugs, Bollard decided to try a different strategy—one that employs the body’s own cells to fight off infection. To accomplish this, she and her colleagues developed killer T cells that, when infused into patients, could protect against three of the most common causes of post-transplant infection: Epstein-Barr virus (EBV), cytomegalovirus (CMV), and adenovirus.

Epstein-Barr virus, which causes mononucleosis, and CMV are commonplace among adults. By age 40, up to 95 percent of adults have been infected with EBV. In most people, EBV causes mild, flu-like symptoms. Thereafter, EBV becomes dormant but can re-emerge in transplant patients, causing serious illness or death. CMV similarly infects and becomes dormant in many people, retaining the potential to cause serious infections—usually affecting the lungs and causing severe pneumonia—in patients with weakened immune systems.

To give patients a better chance for recovery, Bollard partnered with Malcom Brenner, who directs the National Gene Vector Laboratory (NGVL) at Baylor College of Medicine. Brenner used the NCRR-funded laboratory to engineer an adenovirus—a common virus that can infect many different types of cells—to produce proteins from CMV, in addition to adenovirus proteins. This hybrid virus was then used to infect immune cells, called B cells, that were already harboring EBV. When infected, B cells are known to stimulate the growth of killer T cells in tissue culture, which can in turn destroy virus-containing cells.